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Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants

Cardemil, Cristina V; Cao, Yi; Posavad, Christine M; Badell, Martina L; Bunge, Katherine; Mulligan, Mark J; Parameswaran, Lalitha; Olson-Chen, Courtney; Novak, Richard M; Brady, Rebecca C; DeFranco, Emily; Gerber, Jeffrey S; Pasetti, Marcela; Shriver, Mallory; Coler, Rhea; Berube, Bryan; Suthar, Mehul S; Moreno, Alberto; Gao, Fei; Richardson, Barbra A; Beigi, Richard; Brown, Elizabeth; Neuzil, Kathleen M; Munoz, Flor M; ,
BACKGROUND AND OBJECTIVES/UNASSIGNED:Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS/UNASSIGNED:Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS/UNASSIGNED:Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS/UNASSIGNED:Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.
PMID: 38332733
ISSN: 1098-4275
CID: 5632472

SARS-CoV-2 and Influenza A Virus Induce Longitudinal Transcriptomic Changes in Hamster Spinal Cord Tissue

Serafini, Randal A; Frere, Justin J; tenOever, Benjamin; Zachariou, Venetia
PMID: 37389976
ISSN: 1528-1159
CID: 5540612

Inhibiting influenza virus transmission using a broadly acting neuraminidase that targets host sialic acids in the upper respiratory tract

Ortigoza, Mila B; Mobini, Catherina L; Rocha, Hedy L; Bartlett, Stacey; Loomis, Cynthia A; Weiser, Jeffrey N
The ongoing transmission of influenza A viruses (IAV) for the past century continues to be a burden to humans. IAV binds terminal sialic acids (SA) of sugar molecules present within the upper respiratory tract (URT) in order to successfully infect hosts. The two most common SA structures that are important for IAV infection are those with α2,3- and α2,6-linkages. While mice were once considered to be an unsuitable system for studying IAV transmission due to their lack of α2,6-SA in the trachea, we have successfully demonstrated that IAV transmission in infant mice is remarkably efficient. This finding led us to re-evaluate the SA composition of the URT of mice using in situ immunofluorescence and examine its in vivo contribution to transmission for the first time. We demonstrate that mice express both α2,3- and α2,6-SA in the URT and that the difference in expression between infants and adults contributes to the variable transmission efficiencies observed. Furthermore, selectively blocking α2,3-SA or α2,6-SA within the URT of infant mice using lectins was necessary but insufficient at inhibiting transmission, and simultaneous blockade of both receptors was crucial in achieving the desired inhibitory effect. By employing a broadly acting neuraminidase to indiscriminately remove both SA moieties in vivo, we effectively suppressed viral shedding and halted the transmission of different strains of influenza viruses. These results emphasize the utility of the infant mouse model for studying IAV transmission and strongly indicate that broadly targeting host SA is an effective approach that inhibits IAV contagion.IMPORTANCEInfluenza virus transmission studies have historically focused on viral mutations that alter hemagglutinin binding to sialic acid (SA) receptors in vitro. However, SA binding preference does not fully account for the complexities of influenza A virus transmission in humans. Our previous findings reveal that viruses that are known to bind α2,6-SA in vitro have different transmission kinetics in vivo, suggesting that diverse SA interactions may occur during their life cycle. In this study, we examine the role of host SA on viral replication, shedding, and transmission in vivo. We highlight the critical role of SA presence during virus shedding, such that attachment to SA during virion egress is equally important as detachment from SA during virion release. These insights support the potential of broadly acting neuraminidases as therapeutic agents capable of restraining viral transmission in vivo. Our study unveils intricate virus-host interactions during shedding, highlighting the necessity to develop innovative strategies to effectively target transmission.
PMID: 38206008
ISSN: 2150-7511
CID: 5635222

Staphylococcus aureus senses human neutrophils via PerR to coordinate the expression of the toxin LukAB

Savin, Avital; Anderson, Exene E; Dyzenhaus, Sophie; Podkowik, Magdalena; Shopsin, Bo; Pironti, Alejandro; Torres, Victor J
PMCID:10863418
PMID: 38235972
ISSN: 1098-5522
CID: 5635242

Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Axfors, Cathrine; Schmitt, Andreas M; Janiaud, Perrine; Van't Hooft, Janneke; Abd-Elsalam, Sherief; Abdo, Ehab F; Abella, Benjamin S; Akram, Javed; Amaravadi, Ravi K; Angus, Derek C; Arabi, Yaseen M; Azhar, Shehnoor; Baden, Lindsey R; Baker, Arthur W; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marvin A H; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z; Cowan, Lisa N; Dalgard, Olav; de Almeida E Val, Fernando F; de Lacerda, Marcus V G; de Melo, Gisely C; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony C; Hernandez-Cardenas, Carmen M; Hills, Thomas; Hoepelman, Andy I M; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S; Kremsner, Peter G; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J; Meza-Meneses, Patricia; Monteiro, Wuelton M; Morpeth, Susan C; Mourad, Ahmad; Mulligan, Mark J; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A; O'Brien, Sean M; Okeke, Nwora Lance; Perez, Léna; Perez-Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E; Rockhold, Frank W; Rodriguez-Llamazares, Sebastian; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson S; Seto, Todd B; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E; Thirion-Romero, Ireri; Troxel, Andrea B; Tseng, Ting-Yu; Turner, Nicholas A; Ulrich, Robert J; Walsh, Stephen R; Webb, Steve A; Weehuizen, Jesper M; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando G; Zhong, Wu; Moher, David; Goodman, Steven N; Ioannidis, John P A; Hemkens, Lars G
PMID: 38316844
ISSN: 2041-1723
CID: 5632832

Transcription-replication interactions reveal bacterial genome regulation

Pountain, Andrew W; Jiang, Peien; Yao, Tianyou; Homaee, Ehsan; Guan, Yichao; McDonald, Kevin J C; Podkowik, Magdalena; Shopsin, Bo; Torres, Victor J; Golding, Ido; Yanai, Itai
Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription-replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics.
PMID: 38267581
ISSN: 1476-4687
CID: 5625052

Clonal barcoding of endogenous adult hematopoietic stem cells reveals a spectrum of lineage contributions

Feng, Jue; Jang, Geunhyo; Esteva, Eduardo; Adams, Nicholas M; Jin, Hua; Reizis, Boris
The hierarchical model of hematopoiesis posits that self-renewing, multipotent hematopoietic stem cells (HSCs) give rise to all blood cell lineages. While this model accounts for hematopoiesis in transplant settings, its applicability to steady-state hematopoiesis remains to be clarified. Here, we used inducible clonal DNA barcoding of endogenous adult HSCs to trace their contribution to major hematopoietic cell lineages in unmanipulated animals. While the majority of barcodes were unique to a single lineage, we also observed frequent barcode sharing between multiple lineages, specifically between lymphocytes and myeloid cells. These results suggest that both single-lineage and multilineage contributions by HSCs collectively drive continuous hematopoiesis, and highlight a close relationship of myeloid and lymphoid development.
PMCID:10823160
PMID: 38227649
ISSN: 1091-6490
CID: 5626632

Transcription"“replication interactions reveal bacterial genome regulation

Pountain, Andrew W.; Jiang, Peien; Yao, Tianyou; Homaee, Ehsan; Guan, Yichao; McDonald, Kevin J.C.; Podkowik, Magdalena; Shopsin, Bo; Torres, Victor J.; Golding, Ido; Yanai, Itai
Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription"“replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics.
SCOPUS:85183015326
ISSN: 0028-0836
CID: 5629352

Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial

Rouphael, Nadine G; Branche, Angela R; Diemert, David J; Falsey, Ann R; Losada, Cecilia; Baden, Lindsey R; Frey, Sharon E; Whitaker, Jennifer A; Little, Susan J; Kamidani, Satoshi; Walter, Emmanuel B; Novak, Richard M; Rupp, Richard; Jackson, Lisa A; Babu, Tara M; Kottkamp, Angelica C; Luetkemeyer, Anne F; Immergluck, Lilly C; Presti, Rachel M; Bäcker, Martín; Winokur, Patricia L; Mahgoub, Siham M; Goepfert, Paul A; Fusco, Dahlene N; Atmar, Robert L; Posavad, Christine M; Netzl, Antonia; Smith, Derek J; Telu, Kalyani; Mu, Jinjian; McQuarrie, Lisa J; Makowski, Mat; Makhene, Mamodikoe K; Crandon, Sonja; Montefiori, David C; Roberts, Paul C; Beigel, John H
We compared the serologic responses of one versus two doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A two-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.
PMID: 37561027
ISSN: 1537-6613
CID: 5605532

TLR4 sensing of IsdB of Staphylococcus aureus induces a proinflammatory cytokine response via the NLRP3-caspase-1 inflammasome cascade

Gonzalez, Juan José Izquierdo; Hossain, Md Faruq; Neef, Jolanda; Zwack, Erin E; Tsai, Chih-Ming; Raafat, Dina; Fechtner, Kevin; Herzog, Luise; Kohler, Thomas P; Schlüter, Rabea; Reder, Alexander; Holtfreter, Silva; Liu, George Y; Hammerschmidt, Sven; Völker, Uwe; Torres, Victor J; van Dijl, Jan Maarten; Lillig, Christopher H; Bröker, Barbara M; Darisipudi, Murty N
The prevalence of multidrug-resistant Staphylococcus aureus is of global concern, and vaccines are urgently needed. The iron-regulated surface determinant protein B (IsdB) of S. aureus was investigated as a vaccine candidate because of its essential role in bacterial iron acquisition but failed in clinical trials despite strong immunogenicity. Here, we reveal an unexpected second function for IsdB in pathogen-host interaction: the bacterial fitness factor IsdB triggers a strong inflammatory response in innate immune cells via Toll-like receptor 4 and the inflammasome, thus acting as a novel pathogen-associated molecular pattern of S. aureus. Our discovery contributes to a better understanding of how S. aureus modulates the immune response, which is necessary for vaccine development against the sophisticated pathogen.
PMID: 38112465
ISSN: 2150-7511
CID: 5612322